This Research Training Program in Disease Oriented Neuroscience is designed to facilitate the transition between graduate training and a research-based career in neurology. R25 program trainees will receive career mentoring from experienced clinician scientists and basic researchers in Neurology along with research mentoring from clinical and laboratory research faculty in multiple departments and schools within the University of Pennsylvania. A focused educational program drawn from departmental as well as institutional programs will supplement laboratory research has been developed and refined over the prior project period, and includes training in translational research methods, applications, and the responsible conduct of research. The program is conducted in a large research-oriented institution with leading residency programs in adult and child neurology that trains some of the best candidates in the country. Between adult and child neurology, there are over 100 faculty members in our department, ranging from master clinicians, clinical educators, and clinical investigators to physician/scientists and basic scientists. Over 80% of graduating residents over the past 15 years have remained in academic medicine, and many have chosen careers as clinician scientists. The Hospital of the University of Pennsylvania and Children's Hospital of Philadelphia at the Perelman School of Medicine, where most of the clinical residency and fellowship training occurs, are located within a highly compact university campus in West Philadelphia spanning less than one half mile. Penn is also home to the first neuroscience institute in the country, the Mahoney Institute for Neurosciences, which consolidates over 150 faculty members from 32 departments and six schools pursuing neuroscience research at Penn. The range of research opportunities for our R25 trainees can thus be extended to the wider neuroscience community inside and outside the Department of Neurology through co-mentorship of trainees with a diverse array of eminent scientists carrying out research relevant to the NINDS mission to reduce the burden of neurological disease.